A peptide competing with VEGF165 binding on neuropilin-1 mediates targeting of a chlorin-type photosensitizer and potentiates its photodynamic activity in human endothelial cells
Identifieur interne : 001368 ( Main/Exploration ); précédent : 001367; suivant : 001369A peptide competing with VEGF165 binding on neuropilin-1 mediates targeting of a chlorin-type photosensitizer and potentiates its photodynamic activity in human endothelial cells
Auteurs : Loraine Tirand [France] ; Céline Frochot [France] ; Régis Vanderesse [France] ; Noémie Thomas [France] ; Eric Trinquet [France] ; Sophie Pinel [France] ; Marie-Laure Viriot [France] ; Francois Guillemin [France] ; Muriel Barberi-Heyob [France]Source :
- Journal of controlled release [ 0168-3659 ] ; 2006.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
Destruction of the neovasculature is essential for efficient tumor eradication by photodynamic therapy (PDT). Since the over-expression of receptors for vascular endothelial growth factor (VEGF) is correlated with tumor angiogenesis and subsequent growth, we conjugated a photosensitizer (5-(4-carboxyphenyl)-10,15,20-triphenyl-chlorin, TPC), via a spacer (6-aminohexanoic acid, Ahx), to a VEGF receptor-specific heptapeptide (ATWLPPR). ATWLPPR and TPC-Ahx-ATWLPPR bound exclusively to neuropilin-1 (NRP-1) recombinant chimeric protein (IC50=19 and 171 μM, respectively) but were devoid of affinity for VEGF receptor type 2 (VEGFR-2, KDR), to which ATWLPPR was initially thought to bind. TPC-Ahx-ATWLPPR was incorporated up to 25-fold more in human umbilical vein endothelial cells (HUVEC) than TPC over a 24-h period, and the addition of 8 mM ATWLPPR induced a significant decrease of this uptake (P<0.05), corroboraling a receptor-mediated incorporation. Slightly less cytotoxic in the dark, TPC-Ahx-ATWLPPR exhibited enhanced in vitro photodynamic activity (10.4-fold), compared to TPC. Pharmacokinetic analysis in nude mice xenografted with U87 human malignant glioma cells revealed relevant tumor levels as soon as 1 h after intravenous injection of TPC-Ahx-ATWLPPR, and a rapid elimination from the blood compartment. Moreover, TPC-Ahx-ATWLPPR was not degraded in vivo up to 2 h after intravenous injection. Taken together, our results demonstrate that TPC-Ahx-ATWLPPR is a much more potent photosensitizer in vitro than TPC, in NRP-1-expressing cells. Thus, it may efficiently potentiate the vascular effect of PDT in vivo.
Affiliations:
- France
- Grand Est, Languedoc-Roussillon, Lorraine (région), Occitanie (région administrative)
- Bagnols sur Ceze, Nancy, Vandoeuvre-les-Nancy
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wicri:level="3"><inist:fA14 i1="01"><s1>Centre Alexis Vautrin-CRAN, UMR 7039 CNRS-UHP-INPL, Avenue de Bourgogne</s1><s2>54511 Vandoeuvre-les-Nancy</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandoeuvre-les-Nancy</settlement></placeName></affiliation></author><author><name sortKey="Frochot, Celine" sort="Frochot, Celine" uniqKey="Frochot C" first="Céline" last="Frochot">Céline Frochot</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>DCPR-GRAPP, Groupe ENSIC-UMR 7630 CNRS-INPL, 1 Rue Grandville</s1><s2>54000 Nancy</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Vanderesse, Regis" sort="Vanderesse, Regis" uniqKey="Vanderesse R" first="Régis" last="Vanderesse">Régis Vanderesse</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>LCPM, Groupe ENSIC-UMR 7568 CNRS-INPL, 47 Rue Henri Déglin</s1><s2>54000 Nancy</s2><s3>FRA</s3><sZ>3 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Thomas, Noemie" sort="Thomas, Noemie" uniqKey="Thomas N" first="Noémie" last="Thomas">Noémie Thomas</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Centre Alexis Vautrin-CRAN, UMR 7039 CNRS-UHP-INPL, Avenue de Bourgogne</s1><s2>54511 Vandoeuvre-les-Nancy</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandoeuvre-les-Nancy</settlement></placeName></affiliation></author><author><name sortKey="Trinquet, Eric" sort="Trinquet, Eric" uniqKey="Trinquet E" first="Eric" last="Trinquet">Eric Trinquet</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Cis Bio International. Site de Marcoule</s1><s2>30204 Bagnols sur Ceze</s2><s3>FRA</s3><sZ>5 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Languedoc-Roussillon</region><settlement type="city">Bagnols sur Ceze</settlement></placeName></affiliation></author><author><name sortKey="Pinel, Sophie" sort="Pinel, Sophie" uniqKey="Pinel S" first="Sophie" last="Pinel">Sophie Pinel</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Laboratoire d'Histopathologie Expérimentale et Moléculaire, Faculté de Médecine, 9 Avenue de la forêt de Haye, B.P. 184</s1><s2>54505 Vandoeuvre-les-Nancy</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandoeuvre-les-Nancy</settlement></placeName></affiliation></author><author><name sortKey="Viriot, Marie Laure" sort="Viriot, Marie Laure" uniqKey="Viriot M" first="Marie-Laure" last="Viriot">Marie-Laure Viriot</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>DCPR-GRAPP, Groupe ENSIC-UMR 7630 CNRS-INPL, 1 Rue Grandville</s1><s2>54000 Nancy</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Nancy</settlement></placeName></affiliation></author><author><name sortKey="Guillemin, Francois" sort="Guillemin, Francois" uniqKey="Guillemin F" first="Francois" last="Guillemin">Francois Guillemin</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Centre Alexis Vautrin-CRAN, UMR 7039 CNRS-UHP-INPL, Avenue de Bourgogne</s1><s2>54511 Vandoeuvre-les-Nancy</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandoeuvre-les-Nancy</settlement></placeName></affiliation></author><author><name sortKey="Barberi Heyob, Muriel" sort="Barberi Heyob, Muriel" uniqKey="Barberi Heyob M" first="Muriel" last="Barberi-Heyob">Muriel Barberi-Heyob</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Centre Alexis Vautrin-CRAN, UMR 7039 CNRS-UHP-INPL, Avenue de Bourgogne</s1><s2>54511 Vandoeuvre-les-Nancy</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Lorraine (région)</region><settlement type="city">Vandoeuvre-les-Nancy</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of controlled release</title><title level="j" type="abbreviated">J. control. release</title><idno type="ISSN">0168-3659</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of controlled release</title><title level="j" type="abbreviated">J. control. release</title><idno type="ISSN">0168-3659</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding</term><term>Endothelial cell</term><term>Glioma</term><term>Heterograft</term><term>Human</term><term>Peptides</term><term>Pharmaceutical technology</term><term>Photodynamic therapy</term><term>Photosensitizer</term><term>Target</term><term>Targeting</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Peptide</term><term>Liaison</term><term>Ciblage</term><term>Cible</term><term>Photosensibilisant</term><term>Homme</term><term>Cellule endothéliale</term><term>Photothérapie dynamique</term><term>Traitement</term><term>Gliome</term><term>Hétérogreffe</term><term>Technologie pharmaceutique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Destruction of the neovasculature is essential for efficient tumor eradication by photodynamic therapy (PDT). Since the over-expression of receptors for vascular endothelial growth factor (VEGF) is correlated with tumor angiogenesis and subsequent growth, we conjugated a photosensitizer (5-(4-carboxyphenyl)-10,15,20-triphenyl-chlorin, TPC), via a spacer (6-aminohexanoic acid, Ahx), to a VEGF receptor-specific heptapeptide (ATWLPPR). ATWLPPR and TPC-Ahx-ATWLPPR bound exclusively to neuropilin-1 (NRP-1) recombinant chimeric protein (IC<sub>50</sub>=19 and 171 μM, respectively) but were devoid of affinity for VEGF receptor type 2 (VEGFR-2, KDR), to which ATWLPPR was initially thought to bind. TPC-Ahx-ATWLPPR was incorporated up to 25-fold more in human umbilical vein endothelial cells (HUVEC) than TPC over a 24-h period, and the addition of 8 mM ATWLPPR induced a significant decrease of this uptake (P<0.05), corroboraling a receptor-mediated incorporation. Slightly less cytotoxic in the dark, TPC-Ahx-ATWLPPR exhibited enhanced in vitro photodynamic activity (10.4-fold), compared to TPC. Pharmacokinetic analysis in nude mice xenografted with U87 human malignant glioma cells revealed relevant tumor levels as soon as 1 h after intravenous injection of TPC-Ahx-ATWLPPR, and a rapid elimination from the blood compartment. Moreover, TPC-Ahx-ATWLPPR was not degraded in vivo up to 2 h after intravenous injection. Taken together, our results demonstrate that TPC-Ahx-ATWLPPR is a much more potent photosensitizer in vitro than TPC, in NRP-1-expressing cells. Thus, it may efficiently potentiate the vascular effect of PDT in vivo.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Grand Est</li><li>Languedoc-Roussillon</li><li>Lorraine (région)</li><li>Occitanie (région administrative)</li></region><settlement><li>Bagnols sur Ceze</li><li>Nancy</li><li>Vandoeuvre-les-Nancy</li></settlement></list><tree><country name="France"><region name="Grand Est"><name sortKey="Tirand, Loraine" sort="Tirand, Loraine" uniqKey="Tirand L" first="Loraine" last="Tirand">Loraine Tirand</name></region><name sortKey="Barberi Heyob, Muriel" sort="Barberi Heyob, Muriel" uniqKey="Barberi Heyob M" first="Muriel" last="Barberi-Heyob">Muriel Barberi-Heyob</name><name sortKey="Frochot, Celine" sort="Frochot, Celine" uniqKey="Frochot C" first="Céline" last="Frochot">Céline Frochot</name><name sortKey="Guillemin, Francois" sort="Guillemin, Francois" uniqKey="Guillemin F" first="Francois" last="Guillemin">Francois Guillemin</name><name sortKey="Pinel, Sophie" sort="Pinel, Sophie" uniqKey="Pinel S" first="Sophie" last="Pinel">Sophie Pinel</name><name sortKey="Thomas, Noemie" sort="Thomas, Noemie" uniqKey="Thomas N" first="Noémie" last="Thomas">Noémie Thomas</name><name sortKey="Trinquet, Eric" sort="Trinquet, Eric" uniqKey="Trinquet E" first="Eric" last="Trinquet">Eric Trinquet</name><name sortKey="Vanderesse, Regis" sort="Vanderesse, Regis" uniqKey="Vanderesse R" first="Régis" last="Vanderesse">Régis Vanderesse</name><name sortKey="Viriot, Marie Laure" sort="Viriot, Marie Laure" uniqKey="Viriot M" first="Marie-Laure" last="Viriot">Marie-Laure Viriot</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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